CAPSULES
PROF THIRU GOVENDER
PHARMACEUTICAL SCIENCES,
UKZN
CAPSULES
Definition: a dose of one or more
medicinal substance/s enclosed in a hard
or soft gelatin shell.
Advantages
1. Few formulation problems.
2. Better stability than tablets.
3. Reproducible disintegration.
4. Fewer ingredients than tablets → ↓ chance
of interaction and ↓ interference with
bioavailability.
5. Convenient dosage form for many solids
and liquids.
Disadvantages
1. Fairly poor mass control.
2. The unit is not tamper proof.
3. High production cost.
Raw Materials for Gelatin Capsules
Manufacture of hard and soft gelatin capsules
are similar.
Gelatin solution is prepared → add colourants,
preservatives and process aids depending on
the type of capsule required.
1. Gelatin
major component of capsules
possesses 4 basic properties that make it suitable
non-toxic → widely used.
readily soluble in biological fluids at body temperature.
good film forming material.
as a solution in H2O or a H2O-glycerol blend, it undergoes a
reversible phase change from sol to gel at temps only a few
degrees above ambient temperature.
substance of natural origin, but does not occur as
such in nature.
prepared by hydrolysis of collagen which is the main
protein constituent of connective tissue (animal bones
and skins).
2. Plasticizers
soft gelatin capsules required to be flexible.
addition of plasticizers → ↑ flexibility.
proportion of plasticizers → affects
characteristics of capsule e.g. glycerol,
sorbitol, propylene glycol, acacia
3. Colourants
soluble dyes or insoluble pigments
mixtures of dyes → different colours
pigments → iron oxides or titanium dioxide
4. Preservatives
to prevent microbial contamination during
manufacture.
finished capsules do not contain sufficient
moisture to support microbial growth.
soft gelatin capsules may contain an
antifungal to prevent growth on their surfaces
when stored in non-protective package.
Manufacture
Hard capsule shells are made by:
1) dipping moulds into gelatin solution
2) the resulting film on the mould is dried
3) the shell is cut to length and then stripped
from the mould
1 2 3
Sizes (see table)
range of 8 sizes→ from size 000 (largest) to size 5 (smallest)
to determine the size of capsule to be used or the fill weight
for a formulation, the following equation is used:
Capsule fill weight = tapped bulk density x capsule volume
Eg. if powder has a fill weight of 500mg and a tapped bulk
density of 0.80gml-1
Capsule volume required = 0.5g
0.8g/ml
= 0.63ml
therefore use size 0 capsule (vol → 0.67ml) [size rounded up]
Hard Gelatin Capsule Sizes and Fill Volumes
Capsule Fill Volume
Size No. (ml)
5 0.13
4 0.20
3 0.27
2 0.37
1 0.48
0 0.67
00 0.95
000 1.36
Filling
All formulations for filling into capsules must
possess two basic requirements. They must:
be able to be accurately dose into the capsule shell.
release their active contents in a form which is
available to the patient.
dry solids as well as semi-solids (e.g. paste
and thixotropic mixtures) may be filled into hard
gelatin capsules.
Formulation Aspects
powders as well as non-powders (tablets, granules/
pellets, semi-solids) may be used in capsules.
diluents may be required for low dose drugs → can
improve flow by using free-flowing diluents e.g.
maize starch or spray dried lactose.
for high dose drugs → glidants (up to 5% w/w) may
be used to improve flow e.g. colloidal silicon
dioxide.
lubricants may be added to reduce powder to metal
adhesion e.g. Mg stearate.
wetting agents → ↑ release of drug.
Bioavailability Aspects
absorption from capsule → generally more
rapid than tablet → provided that gastric
and intestinal fluids penetrate the contents
after the shell has ruptured.
absorption related to formulation and
preparation.
Formulation Factors
Active (drug)→ particle size, solubility,
crystalline form.
Diluents→ ↑ solubility→ ↑ release of active -
depends on solubility of active as well.
Glidants and lubricants → depends on the
hydrophobicity of these substances.
Wetting agents → ↑ release rate of drug.
Soft Gelatin Capsules
consists of units of continuous gelatin shell
surrounding a liquid fill material.
capsules are formed, filled and sealed in one
operation.
different sizes & shapes.
Advantages
1. no compression required → useful for poorly
compressible drugs.
2. dose content uniformity is optimized → drug
dissolved or dispersed in liquid.
3. drugs can be protected against hydrolysis
and oxidation → use solution or dispersion in
oil.
4. drug dissolved or dispersed in liquid →
break-up of capsule → drug dispersion of
high surface area → good bioavailability.
Formulation of the Gelatin Capsule
Consists of 2 main ingredients: gelatin and
plasticizers (e.g. glycerol)
Water is used to form capsule.
Other additives: preservatives, dyes, flavours.
Formulation of the Capsule Contents
Limitation for fill materials
drugs or excipients containing high concentrations of
H2O or other gelatin solvents cannot be
incorporated.
emulsions are not recommended (o/w or w/o) →
unstable and will crack as the water is lost from the
shell in the manufacturing process.
extremes of pH must be avoided → below pH 2.5
and above pH 7.5
aldehydes must be avoided.
Liquid Vehicles
H2O-immiscible oils → volatile and non-volatile oils
→ fixed and aromatic vegetable oils, hydrocarbons,
liquid ethers and esters.
H2O-miscible liquids → PEG’s (400-600), alcohols,
triacetin.
propylene glycol and glycerol can be used but the
concentration must be low (5-10%)
Suspensions
insoluble drugs → dispersed in the above vehicles
and encapsuled.
suspending agents (beeswax, ethylcellulose,
PEG4000 and 6000) and surfactants (to promote
wetting) are added.
Bioavailability Aspects
yield similar blood levels of drug to those
produced by liquids.
more rapid absorption than tablets.
drugs dissolved in oils or drugs that are oils
and are emulsified → are absorbed from GIT
into lymphatic systems → surface area of
emulsified system is high therefore ↑
dissolution rate → enhanced bioavailability.
Testing of Capsules
1. Uniformity of fill weight
2. Disintegration test
3. Dissolution test
4. Content uniformity